...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of bacteriology >Response of Bacillus subtilis to Cerulenin and Acquisition of Resistance
【24h】

Response of Bacillus subtilis to Cerulenin and Acquisition of Resistance

机译：枯草芽孢杆菌对天青素的反应及耐药性的获得

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Cerulenin is a fungal mycotoxin that potently inhibits fatty acid synthesis by covalent modification of the active site thiol of the chain-elongation subtypes of β-ketoacyl-acyl carrier protein (ACP) synthases. The Bacillus subtilis fabF (yjaY) gene (fabFb ) encodes an enzyme that catalyzes the condensation of malonyl-ACP with acyl-ACP to extend the growing acyl chain by two carbons. There were two mechanisms by which B. subtilis adapted to exposure to this antibiotic. First, reporter gene analysis demonstrated that transcription of the operon containing the fabF gene increased eightfold in response to a cerulenin challenge. This response was selective for the inhibition of fatty acid synthesis, since triclosan, an inhibitor of enoyl-ACP reductase, triggered an increase in fabF reporter gene expression while nalidixic acid did not. Second, spontaneous mutants arose that exhibited a 10-fold increase in the MIC of cerulenin. The mutation mapped at the B. subtilis fabF locus, and sequence analysis of the mutant fabF allele showed that a single base change resulted in the synthesis of FabFb[I108F]. The purified FabFb and FabFb[I108F] proteins had similar specific activities with myristoyl-ACP as the substrate. FabFb exhibited a 50% inhibitory concentration (IC50) of cerulenin of 0.1 μM, whereas the IC50 for FabFb[I108] was 50-fold higher (5 μM). These biochemical data explain the absence of an overt growth defect coupled with the cerulenin resistance phenotype of the mutant strain.
机译：天青蛋白是一种真菌真菌毒素，可通过共价修饰β-酮酰基-酰基载体蛋白（ACP）合成酶链延长亚型的活性位点巯基来抑制脂肪酸的合成。 枯草芽孢杆菌fabF （ yjaY ）基因（ fabF b ）编码一种酶，该酶催化丙二酰-带有酰基ACP的ACP可以将增长的酰基链延长两个碳原子。 B有两种机制。枯草杆菌适合暴露于这种抗生素。首先，记者基因分析表明，含有 fabF 基因的操纵子的转录响应于铜蓝蛋白攻击而增加了八倍。该反应对于抑制脂肪酸的合成具有选择性，因为烯丙基-ACP还原酶的抑制剂三氯生引发了 fabF 报告基因表达的增加，而萘啶酸则没有。其次，出现了自发突变体，其在铜绿素的MIC上显示出10倍的增加。突变位于 B。枯草杆菌fabF 基因座，突变 fabF 等位基因的序列分析表明，单碱基改变导致FabF b [I108F]的合成。以肉豆蔻酰-ACP为底物，纯化的FabF b 和FabF b [I108F]蛋白具有相似的比活性。 FabF b 对青霉素的抑制浓度为50％（IC 50 ）（IC 50 ），而FabF b < / sub> [I108]高50倍（5μM）。这些生化数据解释了不存在明显的生长缺陷以及突变菌株的抗天青素抗性表型。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号